过氧化物酶体增殖物活化受体γ配体激动剂对哮喘大鼠气道平滑肌收缩的影响  

The effect of the ligands agonist of PPAR-γ on the contraction of airway smooth muscle in rats with asthma

作　　者：夏俊杰[1] 黄玲[1] 熊瑛[2] 王开绿[1] 邱宇[3] 郑晓凤[1] 李文军[1] 刘艳群[1] 蒙琴[1] 高峰[1] 

机构地区：[1]绵阳市第三人民医院呼吸内科,四川省621000 [2]泸州医学院附属医院呼吸内科 [3]泸州医学院

出　　处：《中华临床医师杂志（电子版）》2012年第17期5066-5072,共7页Chinese Journal of Clinicians(Electronic Edition)

基　　金：四川省卫生厅科研课题(070207)

摘　　要：目的观察过氧化物酶体增殖物活化受体γ(PPARγ)配体激动剂罗格列酮(RSG)对哮喘大鼠气道平滑肌收缩的影响。方法雄性SD大鼠75只,按随机数字表法分为对照组(A组)、哮喘组(B组)、RSG治疗组(C组),每组25只。制备各组离体去上皮气管环分别为a、b、c组。比较三组大鼠引喘潜伏期差异。(1)比较在0.05 mmol/L、0.5 mmol/L、5 mmol/L浓度乙酰胆碱(ACh)激发下,三组大鼠离体气管环收缩张力大小。(2)比较0.01 mmol/L、0.1 mmol/L、1 mmol/L三种浓度RSG对ACh预收缩的a、b组离体气管环的舒张作用。(3)观察吲哚美辛、亚甲基蓝、普萘洛尔、左旋硝基精氨酸甲(L-NAME)、伊比蝎毒素(IbTX)对RSG舒张a、b组气管环作用的影响。(4)观察三种浓度RSG对a、b组离体气管环ACh量效曲线的影响。结果三组大鼠引喘潜伏期:B组<C组<A组(均P<0.05)。(1)三组大鼠气管环对ACh的反应率a组<c组<b组(均P<0.05);(2)三种浓度RSG对ACh预收缩的a、b组大鼠离体气管环均有舒张作用(均P<0.05),但三种浓度RSG对a、b组大鼠离体气管环的舒张率差异无统计学意义(均P>0.05);(3)吲哚美辛、L-NAME、亚甲基蓝、普萘洛尔不能阻断a组大鼠气管环RSG引起的舒张(均P>0.05),L-NAME能阻断b组RSG引起的舒张,IbTX对a组和b组RSG引起的舒张均有阻断作用,且对a组的阻断作用更强(均P<0.05);(4)RSG可引起a、b两组大鼠离体气管环ACh量效曲线右移(均P<0.05)。结论 RSG延长哮喘发作潜伏期,降低ACh所引起的气道收缩张力,RSG对大鼠气管环可产生舒张作用,此作用可能与前列环素、胞浆可溶性鸟苷酸环化酶、β2肾上腺素受体无关,而可能与大电导钙激活钾通道、一氧化氮有关。Objective To research the effect of rosiglitazone(RSG),the ligands agonist of peroxisome proliferator-activated receptor γ(PPARγ),on the airway smooth muscle contraction in rats with asthma.Methods Seventy five male SD rats were randomly divided into control group(group A),asthma group(group B),RSG treatment group(C group),twenty five of each group,isolated tracheal rings of rats without epithelium,were prepared as group a,group b,and group c.The latent period of asthma in three groups rats was measured.(1)The contraction tension which were induced by the concentration gradient of Acetycholine(ACh)(0.05 mmol/L,0.5 mmol/L,5 mmol/L)on the isolated tracheal ring in three groups were compared.(2)The relaxing effect on isolated rings in rats from group a and group b,which were precontracted by ACh with three different concentration gradient of RSG,0.01 mmol/L(low density),0.1 mmol/L(middle density),and 1 mmol/L(high density)was compared.(3)The effect on tracheal rings in group a and group b relaxed by the RSG by using Indomethacin,Methylene blue,Propranolol,L-NAME,and IbTX were observed.(4)The effect on the ACh dose-response curves of isolated tracheal rings in rats from group a and group b caused by three different concentration gradient of RSG,0.01 mmol/L,0.1 mmol/L and 1 mmol/L were observed.Results The latent periods of asthma were group B<group C<group A(all P<0.05).(1)The response rates of tracheal rings in rats were group a<group c<group b,which were induced by the concentrations of ACh,and there were significant differences(all P<0.05,n=20).(2)There were relaxed effect on tracheal rings in rats from group a and group b with the concentrations gradient of RSG,furthermore,dose-dependent manner(all P<0.05).However,there were no significant differences in the relaxing effect on group a and group b(all P>0.05,n=20).(3)Indomethacin,Methylene blue and Propranolol had no effect on the relaxation,induced by the concentration gradient of RSG to tracheal rings in rats from group a and group b(all P>0.05);L-NAME had blo

关 键 词：哮喘 PPARΓ 气道 罗格列酮 

分 类 号：R562.25[医药卫生—呼吸系统]